It work to date, we have identifed component neurons of an endogenous opioid mediated analgesia system. These neurons, located in the brainstem, appear to directly control pain-transmission at spinal cord levels. We shall test the hypothesis that these neurons operate under physiological conditions to suppress pain and that they are crucial to the analgesia produced by systemic opiates. We will develop a more precise map of pain-suppresssng cells and investigate them in several ways. First, by recording from them chronically in unanesthetized rats we shall study their responses to various physiological stimuli and to systemic opiate administration. We are particularly interested in direct correlations of activity in these neurons with "analgesic behaviors". Second, using immunohistochemical techniques we will determine which transmitters are present in these neurons. We are particularly interested in the enkephalins, beta-endorphin, and serotonin. Third, we will use several approaches to determine the neural mechanism by which these neurons inhibit pain transmission. We will specifically test the hypothesis that an enkephalinergic interneuron mediates presynaptic inhibition of pain transmitting primary afferent fibers. These studies should contribute to our understanding of the neurochemical, behavioral and physiological basis of the analgesic response of a subject to opiate administration.